Judah Folkman Interview (page: 5 / 6) Cancer Research	Print Interview

There must have been dark moments, moments of self-doubt, fear of failure?

Judah Folkman: Right. Very early in the '70s, there was a time when all of our grants were turned down, so we didn't have any funding. In a university laboratory, if you don't have funding, they cannot carry you. So you must close your laboratory, and you have to stop. Now once you stop, you can't get started so easily because they say, "Well, there are lots of people. These ideas didn't turn out." And there was another time.

Get the Flash Player to see this video. In the '70s, there was post doctoral fellows who would apply, who were told not to come to our laboratory. They said, "That's very controversial, very controversial," and so nothing scares a young post-doc worse than "very controversial," because he doesn't want to commit his two years of his life, three years. And I remember it turned around with a couple of people. One was Michael Gimbroni, but another one was Robert Langer. Robert Langer came from MIT, number one in his class in chemical engineering in 1974. And we really needed help in chemical engineering, because we were trying to get these molecules to diffuse like tumors. And Langer said he had offers from everywhere, from MIT, from Shell Oil, from everywhere. And he was interested in biomedicine, and he was just going to stop in and say hello, but he said, "I have to warn you, I've been told by four professors at MIT don't come here, and never go to a medical school anyhow because they'll treat you like a technician if you're a chemical engineer." And I remember saying, "Why don't you come for six months and make up your own mind?" And that appealed to him, and he came and stayed two years, and within six years was a professor at MIT.

[ Key to Success ] Courage

He was the youngest member of the National Academy of Sciences. He's very famous now.

There had to be something beyond the courage of your scientific convictions. It takes a certain inner strength. What did it take for you to ignore the nay-sayers? Ordinary people would have given up somewhere along the line.

Judah Folkman: When you're a surgeon, you can take somebody through surgery and take care of them, but if anything happens to them it's your fault. It's not the team. And you see what cancer is like.

There are two other things that helped. A lot of credit goes to the Harvard Medical School. They gave me tenure very, very early. Dean Hebert was the deana at the time. I finished my chief residency in 1965 at Mass General, so my surgical training was complete and I was an instructor on the faculty. That's the lowest you can be, and the next level would be assistant professor in six years, associate professor in four to six years, and then tenure at Harvard is given to very few people. The joke at Harvard is that more people die waiting for tenure than for a liver transplant. That's because it takes a long time.

I was only 33 and I was offered the position of professor. I jumped. I was never an associate. They had a position open which was chief surgeon at Children's Hospital. I was told by the dean that this work was very controversial, but that if we were right, Harvard would get the credit, and it would be a new field. And I remember him saying, "The purpose of tenure is not financial security. The purpose is so that you can pursue a wild idea and not lose your job." So that really helped.

There was another time in the mid-'70s. The National Cancer Institute has supported this work virtually uninterrupted for 30 years, so they deserve enormous credit, but there were times when the peer reviewers, who are colleagues, just said, "Don't fund it." There was one time where they turned off all the grants.

The executive secretary came up to Boston and said she didn't think that the study section had been fair. She said she was going to take it all the way to the top, and she did. She took it to the Science Advisory Board. Mary Lasker was on the board and overruled the study section and we got the grant so we could keep going. So there were lots of people involved.

Another one has been Collette Freeman. She's been the executive secretary of our grants for about 15 or more years, and she's known as the mother of angiogenesis research. She made sure that these things were fair. If they were turned down, she would tell us why, and how we had to improve it. Very helpful.

Reading about what you discovered, it seems so simple.

Judah Folkman: The idea is simple, but the figuring it out was extremely complicated. For example,

Get the Flash Player to see this video. Clotting of blood, going from liquid to clotting, is a very simple process when you look at it. But it has 40 proteins. They each have their own genes, receptors, signal transduction, and it's taken 40 years to figure it out. Many, many careers have failed and many have succeeded. And the angiogenic process, just making a capillary grow, is astoundingly complex as you get into it. And if you don't get into it, you can't turn it off, because you've got to know the wiring and the logic. But just how to make a tube, just making a tube, is an incredible set of genes. Then making a branch is an incredible set of genes. And if you look at this system, for example, in the embryo, in a fetus, in a chicken embryo where you can see it. Day one: the heart is not beating, the heart is forming, and all of the blood vessels are forming. But by day two, all of the blood vessels, far out in the limbs and everywhere are all formed, and the whole system is connected, and everything is sealed. And then a signal is sent that the heart can start.

Now that's all a genetic program. In a few percent of all cases, the signal comes early. The heart starts and there's bleeding in some far out place, and the animal dies, and that's the most common cause of miscarriage. Now figuring out how that works is one part of it, and then figuring out what are the chemical signals that a tumor makes that normal cells don't make, and what turns that on. Why?

Get the Flash Player to see this video. In colon cancer, can you have that little tumor for 10, 15, we now know 20 years, and then one day it starts to bring in blood supply, and then you have blood in the stool, and then you have metastases. And then you only have two years left, or three years. That switch now is understood, is being worked out. And turning it off, because it's relentless when tumors turn it on, is incredibly complicated.

The biggest surprise of all, I think, was O'Reilly's discovery with us in 1993, when we found proteins in the body, hidden inside of other proteins, that by themselves, single protein angiostat, can turn the whole process off completely. No matter what the tumor was putting out, all of its angiogenic stimulators, this protein, if you gave it in high enough amount, would just shut it off with no side effects. And then the tumor would come down. It's a big shock, those kinds of things.

Judah Folkman Interview, Page: 1   2   3   4   5   6